NM_139281.3:c.1797-30A>G

Variant names:

• chr5-111118983-A-G
• rs17553936
• NM_139281.3:c.1797-30A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_139281.3(WDR36):​c.1797-30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,558,054 control chromosomes in the GnomAD database, including 77,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (6113 hom., cov: 32)
  • Exomes 𝑓: 0.31 (71735 hom.)
• Consequence: WDR36 NM_139281.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.244
• Publications: 15 publications found

Genes affected

WDR36 (HGNC:30696): (WD repeat domain 36) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Mutations in this gene have been associated with adult-onset primary open-angle glaucoma (POAG). [provided by RefSeq, Jul 2008]

WDR36 Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, G

  Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-111118983-A-G is Benign according to our data. Variant chr5-111118983-A-G is described in ClinVar as Benign. ClinVar VariationId is 1289469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139281.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	NM_139281.3	MANE Select	c.1797-30A>G		intron	N/A	NP_644810.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR36	ENST00000513710.4	TSL:1 MANE Select	c.1797-30A>G		intron	N/A	ENSP00000424628.3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39984 AN: 151916 Hom.: 6117 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.286

GnomAD2 exomes AF: 0.330 AC: 82526 AN: 250268 AF XY: 0.335

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.427

Gnomad ASJ exome AF: 0.391

Gnomad EAS exome AF: 0.245

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.313 AC: 440489 AN: 1406020 Hom.: 71735 Cov.: 23 AF XY: 0.317 AC XY: 223070 AN XY: 703002

African (AFR) AF: 0.0987 AC: 3181 AN: 32242

American (AMR) AF: 0.414 AC: 18469 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 10092 AN: 25786

East Asian (EAS) AF: 0.241 AC: 9498 AN: 39346

South Asian (SAS) AF: 0.403 AC: 34311 AN: 85124

European-Finnish (FIN) AF: 0.392 AC: 20750 AN: 52934

Middle Eastern (MID) AF: 0.399 AC: 2253 AN: 5642

European-Non Finnish (NFE) AF: 0.305 AC: 323938 AN: 1061774

Other (OTH) AF: 0.307 AC: 17997 AN: 58550

GnomAD4 genome AF: 0.263 AC: 39968 AN: 152034 Hom.: 6113 Cov.: 32 AF XY: 0.270 AC XY: 20069 AN XY: 74282

African (AFR) AF: 0.107 AC: 4428 AN: 41528

American (AMR) AF: 0.324 AC: 4940 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3466

East Asian (EAS) AF: 0.256 AC: 1320 AN: 5158

South Asian (SAS) AF: 0.394 AC: 1899 AN: 4822

European-Finnish (FIN) AF: 0.406 AC: 4284 AN: 10556

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.306 AC: 20811 AN: 67936

Other (OTH) AF: 0.282 AC: 594 AN: 2108

Alfa AF: 0.292 Hom.: 1607

Bravo AF: 0.250

Asia WGS AF: 0.297 AC: 1032 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Glaucoma 1, open angle, G Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17553936; hg19: chr5-110454681; COSMIC: COSV72605300;